Analysis of molecular mechanisms of inner ear development by characterizing a secreted molecule, OC29, isolated from rat otocyst.

哺乳动物的内耳由六个不同的感觉器官组成：半规管的三个隆起，球囊和椭圆形的两个斑点，以及耳蜗部的Corti器官。尽管内耳很复杂，但它来自一种简单的环状结构，称为耳囊。然而，内耳发育的分子机制在很大程度上是未知的。为了鉴定与耳囊形成和/或进一步分化有关的分子(S)，我们用信号序列捕捉法从大鼠耳囊cDNA库中分离到一个分泌型分子OC29。OC29被发现是人WFIKKN的大鼠同源物。OC29在发育中的内耳和背神经管中优先表达。在内耳中，OC29的表达在胚胎11.5天(E11.5)时首次检测到，广泛地分布在耳囊的背外侧区域，形成了前庭器官。在E12.5，OC29的表达局限于假定的感觉器官，主要限于BMP4阳性的假定的棘突，并在后期表达减弱。这些结果提示OC29可能参与了内耳感觉器官的早期发育，特别是在半规管嵴的形成过程中。

The mammalian inner ear consists of six distinct sensory organs : three cristae of the semicircular canals, two maculae of the saccule and utricle, and the organ of Corti of the cochlea. Despite its complexity, the inner ear derives from a simple cyctic structure known as an otocyst. However, molecular mechanisms underlying inner ear development are largely unknown. To identify molecule(s) involved in the formation and/or further differentiation of the otocyst, we isolated a secreted molecule, OC29, from a rat otocyst cDNA library by the signal sequence trap method. OC29 was revealed to be a rat homologue of human WFIKKN. OC29 is preferentially expressed in the developing inner ear and dorsal neural tube. In the inner ear, the expression of OC29 is first detectable at embryonic day 11.5 (E11.5), broadly in the dorsolateral region of the otocyst, which gives rise to the vestibular organ. At E12.5, the expression of OC29 becomes restricted to the presumptive sensory organ, mainly to the BMP4-positive presumptive cristae, and expression becomes reduced at later stages. These results suggested that OC29 may have a role in the early development of the inner ear sensory organ, particularly in the formation of the cristae of the semicircular canals.